rs2232784

Variant names:

• chr19-8303874-G-A
• rs2232784
• NM_016579.4:c.483C>T

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BA1

The NM_016579.4(CD320):​c.483C>T​(p.Ser161Ser) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0502 in 1,602,380 control chromosomes in the GnomAD database, including 4,805 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.11 (2042 hom., cov: 33)
  • Exomes 𝑓: 0.043 (2763 hom.)
• Consequence: CD320 NM_016579.4 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: 0.953

Genes affected

CD320 (HGNC:16692): (CD320 molecule) This gene encodes the transcobalamin receptor that is expressed at the cell surface. It mediates the cellular uptake of transcobalamin bound cobalamin (vitamin B12), and is involved in B-cell proliferation and immunoglobulin secretion. Mutations in this gene are associated with methylmalonic aciduria. Alternatively spliced transcript variants encoding different isoforms have been found for this gene.[provided by RefSeq, Jan 2011]

ACMG classification

Verdict is Benign. Variant got -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BP6: Variant 19-8303874-G-A is Benign according to our data. Variant chr19-8303874-G-A is described in ClinVar as [Benign]. Clinvar id is 136681.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr19-8303874-G-A is described in Lovd as [Likely_benign].
• BP7: Synonymous conserved (PhyloP=0.953 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.299 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CD320	NM_016579.4	c.483C>T	p.Ser161Ser	synonymous_variant	Exon 3 of 5	ENST00000301458.10	NP_057663.1
CD320	NM_001165895.2	c.357C>T	p.Ser119Ser	synonymous_variant	Exon 2 of 4		NP_001159367.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CD320	ENST00000301458.10	c.483C>T	p.Ser161Ser	synonymous_variant	Exon 3 of 5	1	NM_016579.4	ENSP00000301458.4

Frequencies

GnomAD3 genomes AF: 0.114 AC: 17408 AN: 152184 Hom.: 2034 Cov.: 33

Gnomad AFR AF: 0.303

Gnomad AMI AF: 0.0230

Gnomad AMR AF: 0.0688

Gnomad ASJ AF: 0.0579

Gnomad EAS AF: 0.0880

Gnomad SAS AF: 0.0395

Gnomad FIN AF: 0.0297

Gnomad MID AF: 0.0696

Gnomad NFE AF: 0.0347

Gnomad OTH AF: 0.104

GnomAD3 exomes AF: 0.0568 AC: 13061 AN: 229976 Hom.: 830 AF XY: 0.0515 AC XY: 6437 AN XY: 124874

Gnomad AFR exome AF: 0.304

Gnomad AMR exome AF: 0.0448

Gnomad ASJ exome AF: 0.0633

Gnomad EAS exome AF: 0.0868

Gnomad SAS exome AF: 0.0352

Gnomad FIN exome AF: 0.0263

Gnomad NFE exome AF: 0.0340

Gnomad OTH exome AF: 0.0467

GnomAD4 exome AF: 0.0435 AC: 63056 AN: 1450078 Hom.: 2763 Cov.: 32 AF XY: 0.0423 AC XY: 30457 AN XY: 720494

Gnomad4 AFR exome AF: 0.311

Gnomad4 AMR exome AF: 0.0475

Gnomad4 ASJ exome AF: 0.0608

Gnomad4 EAS exome AF: 0.0720

Gnomad4 SAS exome AF: 0.0341

Gnomad4 FIN exome AF: 0.0282

Gnomad4 NFE exome AF: 0.0344

Gnomad4 OTH exome AF: 0.0594

GnomAD4 genome AF: 0.115 AC: 17439 AN: 152302 Hom.: 2042 Cov.: 33 AF XY: 0.113 AC XY: 8436 AN XY: 74470

Gnomad4 AFR AF: 0.303

Gnomad4 AMR AF: 0.0687

Gnomad4 ASJ AF: 0.0579

Gnomad4 EAS AF: 0.0882

Gnomad4 SAS AF: 0.0393

Gnomad4 FIN AF: 0.0297

Gnomad4 NFE AF: 0.0347

Gnomad4 OTH AF: 0.102

Alfa AF: 0.0669 Hom.: 473

Bravo AF: 0.127

Asia WGS AF: 0.0820 AC: 285 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:1

Nov 26, 2013

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -

Methylmalonic acidemia due to transcobalamin receptor defect Benign:1

Feb 02, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

not provided Benign:1

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	6.5
DANN	Benign	0.80
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs2232784; hg19: chr19-8368758;